Current treatments for viral disease, e.g., human immunodeficiency virus (HIV), include inhibitors of proteases, e.g., HIV proteases; but these inhibitors can have severe side effects. Also, there has been a rapid emergence of viral, e.g., HIV, strains that are drug resistant, e.g., insensitive to currently used viral protease inhibitors, including HIV protease inhibitors.
HIV-1 protease, an aspartyl protease, is required for the efficient processing of the Gag and Gag-Pol precursor polyproteins; a critical step in the viral life cycle. For this reason, targeting protease has long been the focus of anti-retroviral therapy. However, aside from its proteolytic activity, its effects on the host cell are still unclear. Cytotoxic effects, together with instability, render expression of protease in mammalian cells difficult. Elucidating the role of protease in the viral life cycle, as well as discerning its effects on the host machinery, is vital for the design of novel therapeutic approaches. A processive HIV-1 RNA-dependent RNA polymerase prone to errors, the emergence of resistant strains, and lack of vaccines, highlight the need for novel antivirals and innovative methods to facilitate their discovery.